Hormone-refractory prostate cancer (HRPC) is a leading cause of aging-related cancer and death in men. Normal prostatic cell growth is controlled by androgens, whereas prostate cancer often occurs when this control is disturbed as one ages. The mainstay treatment of androgen-dependent prostate cancer is to remove androgen stimulation by surgery or by hormonal therapy, which, although is temporarily effective, eventually results in a deadly androgen-independent cancer transformation. To understand this cancer transformation mechanism, several microarray studies have been performed to profile specific gene and microRNA expression patterns in relation to HRPC progression in vivo (1, 2, 3). These studies all showed that expression of non-coding RNAs was highly correlated to the degree of tumor differentiation in human prostate cancer. However, in the absence of tissue-specific expression patterning analysis and functional validation, the functions of these microarray-identified non-coding RNAs have not been confirmed by experiments.
MicroRNA (miRNA) is an abundant class of small non-coding RNAs sized about 17 to 25 nucleotides in length, capable of degrading mRNA or suppressing translation of the targeted genes with high sequence complementarity. In cancers, they are involved in suppression of oncogenes or tumor suppressor genes via complementary binding to their targeted gene transcripts, resulting in gene silencing, that results in changes in cellular tumorigenecity (4). Given that cancer progression is a multi-step process involving changes of various oncogene and tumor suppressor gene expressions, the approach to define a certain miRNA function in modulating these tumorigenetic changes can be complicated by the fact that most miRNAs have several or even several tens of targets, moreover, some of which are targeted more strongly than others. Although current computer programs provide a easy way to predict the potential miRNA targets as well as the possible base-pairs of miRNA-target binding, a simple search for sequence complementarity is not sufficient to pin-point the exact interaction between a specific miRNA and its real target(s).